The nature of the chromophore responsible for naturally occurring fluorescence in mouse skin

111

The kinetics of fluorescence in tumour (TT) and subcutaneous tissue (ST) and the vascular effects of photodynamic therapy (PDT) were studied using protoporphyrin IX (PpIX), endogenously generated after i.v. administration of 100 and 200 mg kg-1 5-aminolaevulinic acid (ALA). The experimental model was a rat skinfold observation chamber containing a thin layer of ST in which a small syngeneic mammary tumour grows in a sheet-like fashion. Maximum TT and ST fluorescence following 200 mg kg-1 ALA was twice the value after 100 mg kg-1 ALA, but the initial increase with time was the same for the two doses in both TT and ST. The fluorescence increase in ST was slower and the maximum fluorescence was less and appeared later than in TT. Photodynamic therapy was applied using green argon laser light (514.5 nm, 100 J cm-2). Three groups received a single light treatment at different intervals after administration of 100 or 200 mg kg-1 ALA. In these groups no correlation was found between the fluorescence intensities and the vascular damage following PDT. A fourth group was treated twice and before the second light treatment some fluorescence had reappeared after photobleaching due to the first treatment. Only with the double light treatment was lasting TT necrosis achieved, and for the first time with any photosensitiser in this model this was accomplished without complete ST necrosis. Images Figure 4

Section: Fluorescence Kinetic Studiesmentioning

confidence: 99%

In vivo fluorescence kinetics and photodynamic therapy using 5-aminolaevulinic acid-induced porphyrin: increased damage after multiple irradiations

Veen¹,

Leengoed²,

Star³

1994

111

“…British Journal of Cancer (1997) 75(6) (Weagle et al, 1988) that mice fed on laboratory chow containing chlorophyll have varying amounts of a chlorin-like metabolite in their gastrointestinal tract and sometimes in their skin. In agreement with these results, we found chlorin-like fluorescence emission spectra in tissue extracts from the intestines and skin of non-injected mice.…”

Section: Tumour: Normal Tissue Ratios Of 1251mentioning

confidence: 99%

Biodistribution of charged F(ab')2 photoimmunoconjugates in a xenograft model of ovarian cancer

Duska

Hamblin²,

Bamberg³

et al. 1997

Summary The effect of charge modification of photoimmunoconjugates (PICs) on their biodistribution in a xenograft model of ovarian cancer was investigated. Chlorin.6 e6 was attached site specifically to the F(ab')2 fragment of the murine monoclonal antibody OC125, directed against human ovarian cancer cells, via poly-1-lysine linkers carrying cationic or anionic charges. Preservation of immunoreactivity was checked by enzyme-linked immunosorbent assay (ELISA). PICs were radiolabelled with 1251 and compared with non-specific rabbit IgG PICs after intraperitoneal (i.p.) injection into nude mice. Samples were taken from normal organs and tumour at 3 h and 24 h. Tumour to normal 1251 ratios showed that the cationic OC1 25F(ab')2 PIC had the highest tumour selectivity. Ratios for ce6 were uniformly higher than for 1251, indicating that ce6 became separated from 1251. OC1 25F(ab')2 gave highest tissue values of 1251, followed by cationic OC1 25F(ab')2 PIC; other species were much lower. The amounts of cee delivered per gram of tumour were much higher for cationic OC125F(ab')2 PIC than for other species. The results indicate that cationic charge stimulates the endocytosis and lysosomal degradation of the OC1 25F(ab')2-pl-cee that has bound to the i.p. tumour. Positively charged PICs may have applications in the i.p. photoimmunotherapy of minimal residual ovarian cancer.

“…The prominent peak at 672 nm, with a minor peak above 700 nm ( Figure 2B), may be attributed to degradation products of chlorophyll a from the mouse food pellets. The products mainly responsible for the fluorescence are pheophorbide a and/or pheophytin a (Weagle et al, 1988). On fluorescence analysis, the food pellets were confirmed to contain large amounts of chlorophyll.…”

Section: Discussionmentioning

confidence: 95%

Laser-induced fluorescence studies of the biodistribution of carotenoporphyrins in mice

Nilsson

Johansson²,

Svanberg³

et al. 1997

Summary The biodistribution of two recently developed tumour markers, trimethylated (CP(Me)3) and trimethoxylated (CP(OMe)3) carotenoporphyrin, was investigated by means of laser-induced fluorescence (LIF) after i.v. injection into 38 tumour-bearing (MS-2 fibrosarcoma) female Balb/c mice. At 3, 24, 48 or 96 h after administration, the carotenoporphyrin fluorescence was measured in tumoral and peritumoral tissue, as well as in the abdominal, thoracic and cranial cavities. The fluorescence was induced by a nitrogen laser-pumped dye laser, emitting light at 425 nm, and analysed by a polychromator equipped with an image-intensified CCD camera. The fluorescence was evaluated at 490, 655 and 720 nm: the second and third wavelengths represent the carotenoporphyrin (CP)-related peaks, whereas the first one is close to the peak of the tissue autofluorescence. The tumour and the liver were the two tissue types showing the strongest carotenoporphyrin-related fluorescence, whereas the cerebral cortex and muscle consistently exhibited weak substance-related fluorescence. In most tissue types, the fluorescence intensities decreased over time. A few exceptions were observed, notably the liver, in which the intensity remained remarkably constant over the time period investigated.